The present proposal is a continuation of an inquiry into the metabolism and functions of tissue phosphoproteins. Studies of nuclear proteins such as histones, non-histone acidic proteins, and phosphoproteins may be of importance in understanding the molecular mechanisms underlying the control of transcription in cells. Besides histones, attention is currently focused on the non-histone acidic proteins which appear to be tissue and species specific, and are the predominant source of nuclear phosphoproteins. Associated with them are multiple protein phosphokinases which may be involved in the modification of nuclear proteins and thus serve an important regulatory function(s) in the chain of events related to gene action. Since the development and activity of rat ventral prostate is under the strict physiological regulation by androgenic hormones, the present studies are designed to examine the nature and the hormonal control of nuclear non-histone phosphoproteins in this tissue. Studies are proposed to examine biosynthesis of nuclear non-histone proteins, their phosphorylation, the enzymes involved in phosphorylation and dephosphorylation reactions, their subnuclear localization, and the role of these phosphoproteins and enzymes, in the mediation of androgen action in the prostate. For these studies normal, aging and hyperplastic rat ventral prostates with varying androgenic status are employed. These studies may enhance our understanding of the factors governing the "target" function of testosterone. Due to lack of availability of good experimental models for human benign prostatic hyperplasia and for prostatic cancer it is proposed to examine some of the above biochemical parameters in "normal", hyperplastic and cancerous human prostate. These studies will include examination of the gel electrophoretic profiles of non-histone proteins, their phosphorylation, activity of protein phosphokinases, phosphatases and proteases of nuclei from the human prostates. It is hoped that the results obtained will uncover differences between these parameters of the nuclear metabolism of normal and neoplastic human prostate, which may potentially be of importance in the understanding and treatment of prostatic carcinoma.